What Is the Smallest Change in Pulse Wave Velocity Measurements That Can Be Attributed With Certainty to Clinical Changes in Arterial Stiffness? A Randomized Cross-Over Study

Abstract

Objective: Pulse wave velocity (PWV), a direct measure of arterial stiffness, is a promising biomarker of cardiovascular risk and a cardiovascular surrogate outcome. However, there is no general agreement on the expected reproducibility of PWV which hampers identification of the smallest change in PWV that is clinically significant. The objectives of this study were to estimate the reproducibility of PWV measurements over the course of two weeks in a diverse group of participants and under experimental conditions that are clinically relevant (two observers, morning/afternoon sessions, different number of visits); and to investigate factors that could reduce this reproducibility. Design and method: Using the SphygmoCor CvMS and Arteriograph devices, we were able to estimate the level of PWV reproducibility as the range of intra-subject values that were observed during the study. Every participant was recorded a total of 12 times with each device, spread out over the course of three visits spaced one week apart, with each visit consisting of two morning and two afternoon recordings. Multilevel mixed-effect models were used to identified factors affecting large discrepancies between consecutive PWV measurements for each device. Results: We show that current guidance on PWV-estimation (at least two PWV measurements, and if their difference exceeds 0.5 m/s, a third measurement) is suboptimal because PWV range for most participants was outside 1 m/s threshold, which has been proposed as minimal clinically-important-difference. The best reproducibility was yielded with median of 4 measurements and 1.1 m/s threshold. Regarding PWV reproducibility and repeatability, which are frequently used interchangeably in studies, while the range showed distinct difference between them, commonly used relative measures of variability, such as coefficient of variability, were comparable. We also found that different physiological variables were predictors of discrepancy between consecutive measurements for two devices, which is likely due to their distinct modes of operation. Conclusions: The evidence base for PWV reproducibility is limited, and more research is needed to deepen our understanding of variation in arterial stiffness over time, as well as fluctuations within a population group and in an intervention setting.